A number of pathological conditions are characterized by a profound aberration in the normal function of the CNS. Such conditions include, for example, epilepsy, stroke, bipolar affective disorder, migraine, anxiety, spasticity, spinal cord injury, chronic neurodegenerative disorder and diseases such as Parkinson's disease, Huntington's disease, and Alzheimer's disease. At the clinical level, these conditions usually respond only to pharmacologic intervention with compounds or substances that possess significant activity at the level of the CNS.
Isovaleramide, isovaleric acid and related compounds have been described for treating abnormalities of the CNS, such as epilepsy. These compounds provide a therapeutic approach by effecting a modulation of CNS activity without producing excessive sedation, muscle weakness, fatigue, teratogenicity or hepatotoxicity.
It has been discovered herein that orally administered isovaleramide has a short half-life in humans. In the absence of an approach to reduce the rate of uptake of drug following administration, the short half-life requires that isovaleramide be administered frequently to sustain a therapeutic concentration of the drug without adverse effects. Frequent dosing schedules increase costs and raise concerns of patient compliance. Thus, it would be desirable to have a sustained-release formulation of isovaleramide, isovaleric acid and related compounds that can be administered on a once or twice per day schedule for the effective treatment of epilepsy and other pathological conditions of the CNS.